The therapeutic use and abuse of opioids has soared in the United States and other countries in recent years. It is estimated that 79.5 million prescriptions for opioid analgesics were filled in 2009 in the US alone. Sales of methadone and oxycodone have increased 1,180% and 730% from 1997 to 2006, respectively. According to a Center for Disease Control (CDC) study, opioid analgesics have contributed to an increasing number of deaths in the United States. The number of fatal opioid analgesic poisonings has increased by 91% between 1999 and 2002. Methadone-related deaths have increased by 390% from 1999 to 2004. Drug overdoses and brain damage associated with long-term drug abuse killed an estimated 37,485 people in 2009. This surpassed the number of deaths attributed to traffic accidents of that year by 1,201. In addition to the human toll, opioid abuse has been estimated to contribute up to $300 billion per year in direct healthcare costs.
Many full opioid receptor agonists such as morphine, methadone, oxycodone and fentanyl are currently in the market for moderate and severe pain management. While these opioid medications provide pain relief to millions of patients, they also cause various devastating side effects. The side effects, which include respiratory depression, addiction, death, constipation and pruritus, are difficult to prevent or treat.
Recently, the use of partial agonists and antagonists as pain medications is increasing in popularity because of their improved side-effect profiles, especially decreased respiratory depression. Within this pharmacological class, buprenorphine is becoming the dominant medication for pain management as a partial agonist and partial antagonist of the mu opioid receptor. However, there are problems associated with the use of buprenorphine. First, buprenorphine is a Drug Enforcement Administration (DEA) schedule III medication whose use and distribution are regulated. Moreover, buprenorphine can cause addition by itself and such addiction is very difficult to manage. Furthermore, its tight binding with the opioid receptor makes it difficult to titrate and it takes 3-5 days for the medication to be eliminated from the body when full agonist opioids are needed for acute pain management and other opioid receptor associated diseases or disorders.
Accordingly, there exists a need for better medications and treatments for preventing or treating opioid receptor associated diseases or disorders.